METHOD FOR PRODUCING DIALYZER COMPRISING A BUNDLE OF HOLLOW FIBERS AND METHOD FOR PRODUCING HOLLOW FIBER

Abstract

A method for producing a hollow fiber pre-product for a dialysis membrane is disclosed. The dialysis membrane includes a distribution of the pore sizes which follows an exponential function such as an e-function. The inverse value of the exponential coefficient (K) is at least 30 nm.sup.2. The dialysis membrane includes at least 50 pores per μm.sup.2 and the share of a free flow area at a surface of the dialysis membrane amounts to at least 2.5%.

Claims

1. A method for producing a hollow fiber of a polymer solution and a precipitating agent comprising the steps of: a) pre-setting selected manufacturing parameters, including parameters of the polymer solution; b) producing a hollow fiber with a nozzle in which a precipitating agent is injected at a predetermined concentration into a ring made of the polymer solution; c) precipitating the hollow fiber in a tempered water bath; d) guiding the hollow fiber through a rinsing bath; e) rinsing the hollow fiber to remove residues of the precipitating in the rinsing bath; f) drying the hollow fiber; g) winding the hollow fiber onto a coil; h) checking current hollow fiber characteristics, with pertinent characteristics including pore size and pore density; i) comparing a current hollow fiber characteristic to a desired hollow fiber characteristic for the extracorporeal blood treatment and a rated range of the hollow fiber characteristic; and j) re-adjusting the selected manufacturing parameters until the current hollow fiber characteristic is within a predefined range of the desired hollow fiber characteristic or the current hollow fiber characteristic is within the rated range of the hollow fiber characteristic.

2. The method according to claim 1, wherein the polymer solution for producing the hollow fiber comprises polysulfone as hydrophobic component.

3. The method according to claim 2, wherein the polymer solution for producing the hollow fiber further comprises polyvinylpyrrolidone (PVP) as hydrophilic component.

4. The method according to claim 3, wherein a proportion of the hydrophobic polymer to the hydrophilic polymer is set to at least one of a predetermined or analytically defined value as the manufacturing parameter.

5. The method according to claim 1, further comprising the step of: winding the hollow fiber in plural layers on the coll.

6. The method according to claim 5, further comprising the step of: accommodating the plural layers of hollow fiber within a casing of a dialyzer, each hollow fiber thereof including pores for the passage of substances being at most medium-molecular, wherein the distribution of the pore sizes at an inner surface of the hollow fiber follows an exponential function and wherein the inverse value of an exponential coefficient (K) is at least 30 nm.sup.2.

7. The method according to claim 6, further comprising the step of: determining the pore size of the hollow fiber.

8. The method according to claim 7, wherein determining the pore size of the hollow fiber comprises: quick-freezing the hollow fiber in liquid nitrogen; breaking the hollow fiber to expose the inner surface of the hollow fiber; and aligning the hollow fiber on an object carrier so that an electron beam of an electron microscope is incident on the inner surface.

9. The method according to claim 8, wherein a share of a free flow area at the inner surface or a blood contact surface of the hollow fiber amounts to at least 2.5%.

10. The method according to claim 7, wherein the pore size is at least 30 nm.sup.2.

11. The method according to claim 10, wherein the pore size is at least 80 nm.sup.2.

12. The method according to claim 7, further comprising the steps of: a) applying the pore size to a histogram and adapting an exponential function to the distribution of the pore size; and b) establishing a number of pores per μm.sup.2 and a free flow area of the inner surface of the hollow fiber as a function of a sum of all pore sizes and the inner surface.

13. The method according to claim 12, wherein the exponential function is an e-function.

14. The method according to claim 6, wherein the exponential coefficient (K) is at least 80 nm.sup.2.

15. The method according to claim 6, wherein the hollow fiber includes at least 50 pores per μm.sup.2.

16. The method of claim 1, wherein the guiding is performed with deflection rollers.

17. The method of claim 1 wherein the pertinent characteristics further include pore size distribution and free flow area.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Hereinafter the present invention will be illustrated in detail by way of a preferred embodiment with reference to the accompanying figures.

[0048] FIG. 1 shows the basic/functional structure of an apparatus for the production of hollow fibers suited for being incorporated in dialyzers,

[0049] FIG. 2 shows the picture of a hollow fiber/membrane according to aspects of the invention by using an electron microscope,

[0050] FIG. 3 shows the mathematical processing of the picture according to FIG. 2 for representing the pores formed in the membrane as well as the pore distribution and

[0051] FIG. 4 shows a histogram drafted from the representation according to FIG. 2 including the pore size distribution.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0052] The method for producing the hollow fiber according to aspects of the invention from a polymer solution and a precipitating agent can be split into the following steps.

[0053] Firstly, a hollow fiber form is produced in a nozzle 1 by injecting in the nozzle 1 the precipitating agent at a predetermined concentration into a ring of a selected (pre-adjusted) polymer solution. Subsequently, the hollow fiber/polymer membrane is precipitated in a tempered water bath 2 below (downstream of) the nozzle 1. Via deflection rollers 4 the hollow fiber is guided through a rinsing bath 6 where it is purified from residues from the preceding process steps. This is followed by a rinsing operation in which the hollow fiber is freed from residues of the precipitating process in the rinsing bath. Finally the now purified hollow fiber is dried in a dryer 8 and is wound onto a coil 10. The winding operation is carried out until the number of hollow fibers corresponding to the dialyzer surface is reached. So far the production method is in conformity with the state of the art.

[0054] The polymer used for producing the hollow fiber preferably is polysulfone is as the hydrophobic component, and polyvinylpyrrolidone (PVP) is preferably used as the hydrophilic component of the polymer. The ratio of the two components is initially set to a predetermined value (empirical value).

[0055] A dialysis membrane is manufactured from the hollow fiber produced in this way by the following steps:

[0056] A hollow fiber bundle (not shown in detail as it is known from the state of the art) is cut out of the hollow fiber wound onto the coil 10. The cut-out hollow fiber bundle is incorporated in a dialyzer casing (equally known from the state of the art and therefore not shown in detail) and serves as dialysis filter.

[0057] In order to safeguard the properties/characteristics of the dialysis membrane, individual parameters, preferably the pore size, or the pore size distribution, of the hollow fiber/membrane is determined and optionally further parameters of the inner face of the hollow fiber are examined by an electron microscope. In this respect, the accompanying FIGS. 2 to 4 are referred to.

[0058] Accordingly, the hollow fibers are detected image-wise by using an electron microscope, wherefrom a surface illustration of the hollow fiber according to FIG. 2, for example, is resulting. This illustration then is subjected to a mathematical processing procedure from which a black-and-white representation approximately according to FIG. 3 is resulting in which only the pores are shown. In this black-and-white representation the pore size as well as the (pore) number thereof can be determined, e.g., by means of pixel numbers or by means of the scale of the picture. Here from a histogram according to FIG. 4 can be established having the pore size distribution by applying for example the “frequency” against the “number of pixels”, wherein alternatively the “number of pixels” could also be replaced by the surface area (nm.sup.2) and could be appropriately converted, as a matter of course.

[0059] In the state of the art verification of these parameters of the dialysis membrane has been implemented not at all or only to a restricted extent/indirectly so far. Therefore in the state of the art only corresponding assumptions have been made about the distribution of the pores in the membrane. Especially, in a simplified manner, a quasi-normal distribution for the pore sizes has been assumed, as the direct influence thereof on the suitability of the hollow fiber for particular purposes (extracorporeal blood treatment) has not been detected or has been underestimated. The pore size therefore was assessed only based on conclusions from the screening characteristics of the membrane. It was not directly measured.

[0060] Rather, in the state of the art, the membrane has been characterized with the screening characteristics of the membrane, namely, by means of the size of the molecules allowed to pass the membrane.

[0061] However, according to aspects of the invention, for the judgment of the produced membrane as to quality and thus for adjusting the hollow fiber production process the pore size of the hollow fiber/membrane is preferably examined by electron-microscopic measuring technology. The characteristic parameters of the inner faces of the fiber can be established by the electron microscope. The direct electron-microscopic visualizing of the pores is at the resolution limit of the current technology and provides substantiated measuring results as a basis of the determination of the characteristic/quality of the hollow fiber and, where appropriate, of the re-adjustment of the manufacturing parameters.

[0062] For sample preparation individual fibers are quick-frozen in liquid nitrogen.

[0063] Subsequently the fibers are broken so as to take pictures of the surface of the fiber inside. Finally, the fiber is aligned on an object carrier so that the electron beam can be directed to the inner face of the fibers.

[0064] Preferably the scanning electron microscope pictures are taken by a scanning electron microscope which is operated, for example, at an accelerating voltage of 3 kV and permits a 50,000 fold magnification. The sample preparation is performed, as afore-mentioned, by quick-freezing of individual hollow fibers in liquid nitrogen, breaking the hollow fibers for exposing the inner face of the hollow fiber so that pictures of the surface of the fiber inside can be taken, and aligning the hollow fiber on an object carrier so that an electron beam of the electron microscope is incident on the inside.

[0065] The distribution of the pore size is shown in a histogram. The pore size distribution in the histogram can be described, in accordance with the invention, again by an e-function, wherein a characteristic parameter of the e-function is used, namely the inverse value of the exponential coefficient (K). The latter can be easily established, as at this point an e-function of the type f(x)=A*ê(−(K)*x) adopts the value {(1/e)*A} (wherein A=maximum value).

[0066] Furthermore, the number of pores per μm.sup.2 can be established and the free flow area of the membrane can be determined as a function of the sum of all pore sizes and a membrane surface. The pore density is the number of the pores per μm.sup.2 and the free flow area puts the sum of all pore sizes in a proportion to the measured surface.

[0067] The hollow fiber/dialysis membrane produced in this way exhibits an exponential function and especially an e-function during distribution of the pore sizes. As particularly suited hollow fibers/dialysis membranes those are selected in which the inverse value of the exponential coefficient (K) of the e-function amounts to at least 30 nm.sup.2 and especially to at least 80 nm.sup.2. The pore density desired especially is at least 50 pores per μm.sup.2 and the share of the free flow area in the total surface area of the dialysis membrane amounts to at least 2.5%.

[0068] Summing up, the membrane according to aspects of the invention comprises the following characteristics: [0069] I. The pore size distribution follows an exponential function. [0070] II. The inverse value of the exponential coefficient (K) amounts to at least 30 nm.sup.2 in the case of high-flux dialyzers and preferably to at least 80 nm.sup.2. [0071] III. The pore density amounts to at least 50 pores/μm.sup.2. [0072] IV. The free flow area amounts to at least 2.5%.

[0073] Hence the invention relates to a dialysis membrane as well as a hollow fiber as pre-product and a method for producing the hollow fiber. The hollow fiber/dialysis membrane according to aspects of the invention includes a distribution of the pore sizes following an exponential function and especially an e-function. The inverse value of the exponential coefficient (K) of the e-function amounts to at least 30 nm.sup.2 and especially to at least 80 nm.sup.2. The hollow fiber/dialysis membrane includes at least 50 pores per μm.sup.2 and the share of a free flow area at a surface of the hollow fiber/dialysis membrane amounts to at least 2.5%.